Directly measuring synaptic and population coupling in cortex during perception The cerebral cortex is the defining brain structure of mammals and underlies our most complex sensory behaviors. A major need exists to identify how synaptic and network mechanisms in cortex lead to normal and impaired sensory perception and behavior. A prevailing model of cortical function postulates that synaptic excitation (E) and inhibition (I) exhibit a stable balance (E/I balance) that is disrupted during sensory impairments and neurodevelopmental diseases. Currently, there is no knowledge regarding synaptic E/I balance during sensory perception, nor its relationship to large-scale neural network activity. We are uniquely positioned to bridge this critical knowledge gap with an innovative combination of whole-cell patch-clamp and large-scale population recordings of defined excitatory and inhibitory neurons during visual perception in mice. This multi- scale approach will enable us to 1) Define how excitatory and inhibitory neuron populations spanning cortical layers predict the accuracy of visual perception 2) Reveal synaptic mechanisms that underlie visual perception 3) Define the relationship between excitatory and inhibitory population activity and synaptic mechanisms engaged by visual perception. SIGNIFICANCE. This project will meet a significant need to understand how excitatory and inhibitory activity in cortex is coordinated at the synaptic, network, and behavioral levels to support sensory perception. It is imperative to understand these processes in individual neurons, networks, and their synaptic inputs during behavior, so that we may better comprehend how to rectify sensory processing deficits characteristic of many neurological and neurodevelopmental disorders. INNOVATION. This project will provide innovative measurements and analysis of the relationship between single-neuron synaptic inputs and large-scale neural network activity during controlled perceptual behaviors. This combination of techniques will allow critical assessment of long-standing theories of cortical function (E/I balance) that require validation in relevant behavioral contexts. These results will provide conceptual innovation by detailing how inhibition sculpts and coordinates excitatory activity in cortex to orchestrate perceptual behaviors.